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 Table of Contents  
Year : 2020  |  Volume : 17  |  Issue : 2  |  Page : 46-48

Correlation of neutrophil–lymphocyte ratio with disease activity in rheumatoid arthritis

Department of Medicine, JNMC, AMU, Aligarh, Uttar Pradesh, India

Date of Submission12-Feb-2018
Date of Acceptance28-Jan-2020
Date of Web Publication14-May-2020

Correspondence Address:
Dr. Ruhi Khan
Department of Medicine, JNMCH, AMU, Aligarh - 202 002, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcls.jcls_16_18

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Background: Neutrophil–lymphocyte ratio (NLR) is reported to be increased in various inflammatory conditions, but its significance in RA remains unclear. The aim of this study was to evaluate whether NLR can be used as a simple tool for disease activity assessment in rheumatoid arthritis (RA). Aim: The aim was to assess the NLR in RA patients and compare between active cases and those in remission. Materials and Methods: The study enrolled 150 diagnosed RA patients. Disease activity was determined with the Disease Activity Score (DAS-28), and the correlation of NLR with disease activity was analyzed. Results: NLR, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were found to be significantly high in RA patients. Further, NLR correlated positively with CRP, ESR, and worsening DAS score. Conclusion: Our study concludes that NLR can become a readily available and cost-effective tool for disease assessment in RA in future.

Keywords: C-reactive protein, Disease Activity Score, erythrocyte sedimentation rate, neutrophil–lymphocyte ratio, rheumatoid arthritis

How to cite this article:
Quaiser S, Khan R. Correlation of neutrophil–lymphocyte ratio with disease activity in rheumatoid arthritis. J Clin Sci 2020;17:46-8

How to cite this URL:
Quaiser S, Khan R. Correlation of neutrophil–lymphocyte ratio with disease activity in rheumatoid arthritis. J Clin Sci [serial online] 2020 [cited 2021 May 16];17:46-8. Available from: https://www.jcsjournal.org/text.asp?2020/17/2/46/284273

  Introduction Top

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation, joint destruction, and a relapsing–remitting course.[1] Currently, disease activity assessment is mainly based on clinical signs and symptoms and laboratory tests. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are well-established indices of inflammation and are widely used for disease activity assessment in RA. Newer laboratory markers are much needed to decrease observer variations. Various previous studies have shown that neutrophil–lymphocyte ratio (NLR) is associated with the prognosis of many inflammatory diseases such as malignancy,[2],[3] chronic kidney disease,[4] acute pancreatitis,[5] and myocardial infarction.[6]

  Materials and Methods Top

This cross-sectional study was carried out in the Rheumatology Clinic, Department of Medicine, Jawaharlal Nehru Medical College, AMU, Aligarh, from January 2015 to November 2017. All patients were diagnosed as RA on the basis of the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR)[7] criteria.[8] Patients were divided into two equal groups (75 patients each) according to the Disease Activity Score (DAS-28):[9] Group A (active) with a DAS28 score ≥2.6 and Group B with a score <2.6 (remission). A control group of fifty age- and gender-matched healthy individuals was also included in our study. Patients suffering from other autoimmune diseases such as systemic lupus erythematosus and inflammatory bowel disease, malignant diseases, hematologic diseases, acute inflammation or other infections, chronic liver disease, and acute or chronic renal failure were excluded from the study. All patients enrolled for the study were subjected to complete hemogram which included estimation of hemoglobin concentration (g/dl), white blood cell count, platelet count, neutrophil (N) count, and lymphocyte (L) counts and calculation of NLR, CRP, and ESR.

Statistical analysis

Statistical analysis was done using SPSS 20, (IBM, United States). The results were expressed as mean ± standard deviation and percentage. Univariate analysis was performed using Chi-square test for categorical variables and one-way ANOVA tests for continuous variables. Pearson's approach was used to quantitate the correlation between variables. “P” < 0.05 was considered statistically significant.

  Results Top

Our study enrolled 150 patients diagnosed with RA on the basis of the ACR/EULAR criteria. Group A included 75 patients with active disease (DAS-28: 4.4 ± 0.6, 3.1–6.0), Group B with 75 patients in remission (DAS-28: 2.0 ± 0.7, 1.2–2.3) (P = 0.001), and Group C with 50 matched controls. The age and gender distribution of the healthy individuals and RA patients was comparable (P > 0.05 for all) as seen in [Table 1].
Table 1: Various laboratory parameters in different study groups

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Observation of the hematological parameters revealed a significant difference among various study groups: it was found that neutrophil counts were statistically significantly higher and absolute lymphocyte counts were statistically significantly lower in patients with RA as compared to healthy controls (P < 0.05 and P < 0.001, respectively). Further, it was seen that CRP and ESR levels significantly increased in patients with active disease (Group A) as compared to those in remission (Group B). Correlation of NLR with ESR, CRP, and DAS-28 (commonly used indices for the assessment of disease activity) showed that NLR was positively correlated with CRP, ESR, and DAS-28 scores (all P < 0.05) as seen in [Table 2].
Table 2: Correlation of neutrophil-lymphocyte ratio with disease parameters in rheumatoid arthritis in active versus inactive disease

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  Discussion Top

RA is a chronic inflammatory multisystem disease, which includes symmetric joint involvement, erosions, and deformities due to synovial inflammation.[10]

In our study, we analyzed the correlation of NLR with the disease activity in RA. The results suggested that NLR was increased in RA patients and positively correlated with CRP, ESR, and DAS-28, which are well-established and commonly used markers for evaluation of disease activity in RA. Our study found that neutrophil counts were increased significantly, whereas the lymphocyte count was decreased significantly in RA patients. The increased neutrophils may be due to the inflammation in RA characterized by increased serum interleukin-6 and tumor necrosis factor-α and other inflammatory factors.[11] These inflammatory factors could promote the maturation and release of neutrophils and platelets from the bone marrow,[12] thus increasing blood neutrophil levels.

Previous studies have also shown similar results like the study by Uslu et al.[13] which reported a significant difference in NLR levels between the patient and control groups and between the active and remission patients. They further reported a significant correlation between NLR and PLR with the DAS-28. Similarly, Tekeoǧlu et al.[14] found that NLR significantly correlated with the DAS-28 of RA patients.

NLR which incorporates the information from neutrophils and lymphocytes has been reported to be associated with the prognosis of various inflammation-related diseases, such as cancer,[15],[16] acute myocardial infarction,[17],[18] and viral infections.[19]

Currently, DAS-28 is the most well-established RA disease activity assessment tool. It consists of the following four domains: (1) number of tender joints of 28 counted, (2) number of swollen joints of 28 counted, (3) ESR, and (4) Visual Analog Scale. As some of these domains are subjective, the interpretation varies between observers.[20] Compared with DAS-28, NLR has advantages, such as it can be calculated without any additional cost because it is derived from parameters which are routinely done in RA patients. Further, it is an objective value that is less likely to be affected by interobserver variation.

Limitations of the study

  1. Due to the limited size of samples, further prospective studies with larger sample sizes are needed to validate the results
  2. The study did not take into account the medications received by the patients, so it does not evaluate the effect of various disease-modifying antirheumatic drugs on hematological parameters
  3. The correlation of NLR with radiological findings also may have provided us some valuable insight into disease activity at an early stage of disease which we plan to include in future assessments.

  Conclusion Top

Our study concludes that NLR is significantly increased in RA patients and can be used as a potential tool for the assessment of disease activity in RA patients, especially in resource-poor settings where the cost of other validated indices and expertise is very scarce.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011;365:2205-19.  Back to cited text no. 1
Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil-lymphocyte ratio: Experience in patients with cancer. Crit Rev Oncol Hematol 2013;88:218-30.  Back to cited text no. 2
Xue TC, Zhang L, Xie XY, Ge NL, Li LX, Zhang BO, et al. Prognostic significance of the neutrophiltolymphocyte ratio in primary liver cancer: A metaanalysis. PLoS One 2014;9:e96072.  Back to cited text no. 3
Kocyigit I, Eroglu E, Unal A, Sipahioglu MH, Tokgoz B, Oymak O, et al. Role of neutrophil/lymphocyte ratio in prediction of disease progression in patients with stage-4 chronic kidney disease. J Nephrol 2013;26:358-65.  Back to cited text no. 4
Azab B, Jaglall N, Atallah JP, Lamet A, Raja-Surya V, Farah B, et al. Neutrophil-lymphocyte ratio as a predictor of adverse outcomes of acute pancreatitis. Pancreatology 2011;11:445-52.  Back to cited text no. 5
Ugur M, Gul M, Bozbay M, Cicek G, Uyarel H, Koroglu B, et al. The relationship between platelet to lymphocyte ratio and the clinical outcomes in ST elevation myocardial infarction underwent primary coronary intervention. Blood Coagul Fibrinolysis 2014;25:806-11.  Back to cited text no. 6
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham 3rd CO, et al. 2010 rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569-81.  Back to cited text no. 7
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24.  Back to cited text no. 8
Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44-8.  Back to cited text no. 9
Sanmartí R, Ruiz-Esquide V, Hernández MV. Rheumatoid arthritis: A clinical overview of new diagnostic and treatment approaches. Curr Top Med Chem 2013;13:698-704.  Back to cited text no. 10
Shimamoto K, Ito T, Ozaki Y, Amuro H, Tanaka A, Nishizawa T, et al. Serum interleukin 6 before and after therapy with tocilizumab is a principal biomarker in patients with rheumatoid arthritis. J Rheumatol 2013;40:1074-81.  Back to cited text no. 11
Hashizume M, Higuchi Y, Uchiyama Y, Mihara M. IL-6 plays an essential role in neutrophilia under inflammation. Cytokine 2011;54:92-9.  Back to cited text no. 12
Uslu AU, Küçük A, Sahin A, Ugan Y, Yilmaz R, Gungor T, et al. Two new inflammatory in- rheumatoid arthritis: Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio. Int J Rheum Dis 2015;18:731-5.  Back to cited text no. 13
Tekeoǧlu İ, Gürol G, Harman H, Karakeçe E, Çiftçi İH. Overlooked hematological markers of disease activity in rheumatoid arthritis. Int J Rheum Dis 2016;19:1078-82.  Back to cited text no. 14
Liu H, Wu Y, Wang Z, Yao Y, Chen F, Zhang H, et al. Pretreatment platelet-to-lymphocyte ratio (PLR) as a predictor of response tofirst-line platinum-based chemotherapy and prognosis for patients with non-small cell lung cancer. J Thorac Dis 2013;5:783-9.  Back to cited text no. 15
Azab B, Mohammad F, Shah N, Vonfrolio S, Lu W, Kedia S, et al. The value of the pretreatment neutrophil lymphocyte ratio vs. platelet lymphocyte ratio in predicting the long-term survival in colorectal cancer. Cancer Biomark 2014;14:303-12.  Back to cited text no. 16
Ghaffari S, Nadiri M, Pourafkari L, Sepehrvand N, Movasagpoor A, Rahmatvand N, et al. The predictive Value of Total Neutrophil Count and Neutrophil/Lymphocyte Ratio in Predicting In-hospital Mortality and Complications after STEMI. J Cardiovasc Thorac Res 2014;6:35-41.  Back to cited text no. 17
Azab B, Shah N, Akerman M, McGinn JT Jr. Value of platelet/lymphocyte ratio as a predictor of all-cause mortality after non-ST-elevation myocardial infarction. J Thromb Thrombolysis 2012;34:326-34.  Back to cited text no. 18
Liu H, Zhang H, Wan G, Sang Y, Chang Y, Wang X, et al. Neutrophil-lymphocyte ratio: A novel predictor for short-term prognosis in acute-on-chronic hepatitis B liver failure. J Viral Hepat 2014;21:499-507.  Back to cited text no. 19
Janta I, Naredo E, Martínez-Estupiñán L, Nieto JC, De la Torre I, Valor L, et al. Patient self-assessment and physician's assessment of rheumatoid arthritis activity: Which is more realistic in remission status? A comparison with ultrasonography. Rheumatology (Oxford) 2013;52:22.  Back to cited text no. 20


  [Table 1], [Table 2]


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